Integration of abnormal macroscopic muscle properties, neuromuscular symptoms and functional capacity in patients post-stroke

State of the art

Stroke is one of the leading causes of physical disability in the world[1]. Approximately 20000 individuals in Belgium suffer from a new or recurrent stroke each year [2]resulting in mild to severe functional disability in daily life in 40% of these patients [3].  According to the World Health Organization, a stroke or Cerebrovascular Accident (CVA) is defined as ‘rapidly developing clinical signs of focal or global disturbance of cerebral function lasting 24 hours or longer or leading to death, with no apparent cause other than of vascular origin’ . In stroke, a lesion of the descending corticospinal system occurs, known as an Upper Motor Neuron (UMN) syndrome.  Damage to the UMN system is further characterized by negative and positive motor signs. Depending on the amount of brain tissue damage and the reorganization within the central nervous system, stroke results in negative and positive motor signs on one side of the body. Negative motor signs are weakness or paralysis, loss of selective control of movement and sensibility disorders. Positive motor signs result from a variety of muscle over activity types such as clonus, co-contractions and spasticity.  Both negative and positive motor signs result in the development of biomechanical changes of the muscles causing secondary  musculoskeletal problems resulting in lifelong changes in motor function. These neural and muscular impairments are a  major source of disability post-stroke. For many of these symptoms there are already well-established treatment methods.  referentie nodig ?  Although the injury initially occurs in the brain, the majority of treatments (such as strengthening, stretching, and tone reduction) are directed at the muscle.  Muscles are one of the most adaptive tissues in the body, as an answer to various positive and negative stimuli, such as disuse and increased activity   An association between post-stroke changes in muscle architecture and clinical symptoms could be a potential tool for prognosis and evaluation of rehabilitation treatment.  Recovery after a stroke is not linear, but follows a curve, with most of the recovery taking place during the first days to months. The recovery process includes four phases, which merge into each other and are not sharply demarcated : the hyperacute/acute (rehabilitation) phase, lasting 0-24 hours, early rehabilitation phase from 24 hours to 3 months, late rehabilitation phase, lasting 3 to 6 months, and chronic phase, lasting longer than 6 months [4]

Morphological muscle and tendon (MMT) characteristics at a macroscopic level can be studied in vivo by means of soft-tissue imaging techniques, such as magnetic resonance imaging (MRI) or ultrasound (US) MRI is expensive, not accessible for everyone and does not allow repositioning of the joints or dynamic imaging. US is a cheaper, accessible, safe and non-invasive method that can be used to look at the MMT characteristics.  In stroke patients, US has been used to measure changes in muscle thickness[5-12], fibre pennation angle [6, 7, 9-13] fascicle length [5, 7, 11, 12, 14], cross-sectional area , echo-intensity [6, 15], tendon length [12, 16, 17] , muscle length [7],  elasticity index and elasticity ratio [13, 15, 18, 19]. All these morphological changes can contribute to greater stiffness, spasticity and reduced strength.  In chronic stroke patient decrease in pennation angle, decrease in fascicle length, decrease in muscle thickness, increase in tendon length, increase in elasticity index and increase in echo-intensity is seen in the spastic paretic limb [5-13, 15-20]. Primarily,  Spasticity has long been assumed to be a major contributing factor to altered MMT characteristics. However, Cerebral Palsy (CP) children with normal muscle tone also show altered muscle growth and reducing spasticity does not seem to sufficiently prevent the development of altered MMT properties. Secondly,do these findings suggest disease-related changes in tissue characteristics , due to sedentary and inactive lifestyle and/or reduced input on the paretic limb and changed neural activation ? Thirdly these MMT changes may suggest  a relationship between changes in muscle architecture and the motor outcome in chronic stroke patients. However these findings cannot be generalized to the entire stroke population due to heterogeneity of the stroke population and limited sample sizes.  

To this date, only few US study’s to define the MMT characteristics in the acute and rehabilitation post-stroke phase have been done. Importantly, no longitudinal investigation using US to measure MMT characteristics in the early stages of stroke has yet been carried out.  There are no studies exploring systematically  the relation between MMT alterations and the timing after the stroke related brain lesion, nor are there any criteria associating relevant changes in MMT  characteristics and clinical implications.

To assess the function of the affected side of the body due to stroke, a variety of assessment tools can be used. Goniometry gives information concerning the active (AROM) and passive (PROM) range of joint motion [21]. Indirect measurement consists of clinical examination of joint ranges but this is subject to a number of systematic and random errors that include intra- and inter-rater errors and variability in goniometric measurement and patient tone[22]

 Muscle strength can be evaluated by the Muscle Research Council scale or dynamometer. [23] Unfortunately, this technique does not distinguish between selective muscle control and the mechanical potential of muscles[22]  The majority of ultrasound study’s to define the MMT changes post-stroke use the (Modified) Asworth Scale or Tardieu Scale as the primary outcome measure for spasticity. (Modified) Asworth Scale and Tardieu are an indicators of resistance to passive muscle stretch and are widely used to measure spasticity. However, spastic muscles mostly develop contractures.  Contractures result in stiffer muscles, which also introduces an increase in resistance to passive muscle stretch. Therefore, changes in resistance to passive muscle stretch may be confounded by changes in the viscoelastic properties of soft tissues and the mechanical characteristics of joint [24] as well as involuntary non velocity dependent background activation of muscles (Figure 1).  Secondly, the validity and reliability of the (Modified) Asworth Scale and Tardieu Scale is insufficient to be used as a measure of spasticity [25-27] In conclusion, all these existing measurement methods cannot differentiate between neurological and biomechanical contributions, nor do they give information about which muscle is most affected.  These clinical measurement methods don’t measure muscle architecture or muscle stiffness. Both characteristics are related to muscle function and the mechanical characteristics of a joint. Therefore, it is important to discriminate any specific neural (disturbed spinal reflex) or non-neural (changed mechanical response of the muscular tissue) contribution.[28]

Better understanding of MMT changes, and how they are related to the timing after stroke and the development of neuromuscular symptoms, has the potential to optimize treatment protocols or develop new treatments after stroke.

The objectives of the research.

The overall goal of this study is to define and differentiate neurological and biomechanical MMT characteristics in the lower limb post-stroke, and exploring their relation to the time after stroke.

To meet the overall goal, six research objectives will be addressed as outlined below.

 1/ To conduct a systematic review  to enhance the evidence-based knowledge concerning macroscopic MMT characteristics post-stroke.

2/ To validate Instrumented spasticity assessment on the lower limb in chronic first-ever stroke patients.

3/ To validate a 3D free-hand Ultrasonography technique to define macroscopic MMT characteristics of the lower limb in chronic first-ever stroke patients.

4/ To define the development of macroscopic MMT characteristics of the lower limb in acute and early rehabilitation phase first-ever stroke patients by a descriptive study.

5/ To define the development of spasticity of the lower limb in acute and early rehabilitation phase  first-ever stroke patients by a descriptive study

6/ To define associations between macroscopic MMT characteristics, the development of neuromuscular symptoms, their relation to the time after stroke and functional outcome of the lower limb in chronic first-ever stroke patients by a mixed longitudinal/cross-sectional study

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